The submandibular gland of the mouse is an exocrine organ for nerve growth factor (NGF) and epidermal growth factor (EGF). Both proteins are synthesized by granular tubule cells (GTC) and ar secreted in large quantities into the saliva. Amylase, a digestive enzyme, is also made by GTC. However, evidence suggests that influences regulating synthesis and secretion of amylase may differ from those controlling growth factors. Human saliva contains EGF- and NGF-like molecules. The biological function of these proteins in saliva is unknown. In this project, we plan to characterize the synthesis to digestive enzymes and growth factors by GTC, clarify the regulation of secretion, and explore possible biological functions that growth factors serve in saliva. Using immunocytochemistry, we intend to determine whether NGF, EGF and amylase are synthesized and packaged the same by GTC. GTC will be experimentally manupulated (hormone administration, starvation) to selectively alter concentrations of the molecules. Secretion will be stumulated pharmacologically with adrenergic (Apha and Beta) and cholinergic secretagogues and concentrations of each molecule in saliva will be measured by radioimmunoassay. In order to determine when the molecules are normally released, secretion will be followed over a 24-hour period and gland levels of the molecules measured by radioimmunoassay. We intend to investigate whether saliva EGF serves as a mitogen in the oral cavity and digestive tract, we will monitor labelling indices in tissues from intact mice, sialoadenectomized mice and sialoadenectomized mice receiving EGF orally. In order to determine if digestive cells have receptors for NGF and EGF, we will introduce ferritin-labelled molecules into the esopohagus, and digestive tissues will be sampled and processed for electron microscopy. Preliminary results suggest that saliva NGF and EGF are absorbed into the portal circulation. These studies will be confirmed and expanded to determine what percent of orally injected protein reaches the portal circulation and if the molecules retain their biological activity after transport. Lastly, we will explore the possibility that NGF and/or EGF participate in wound healing. Purified preparations of the molecules with appropriate controls will be applied to skin lesions in mice and wound contraction followed.